OBJECTIVESIn utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a wide variety of developmental effects in pups at doses much lower than those causing overt toxicity in adult animals. We investigated the relationship between tissue concentrations of TCDD in dams and fetuses and developmental effects on pups.

MATERIALS AND METHODSPregnant Long-Evans rats were given TCDD at a single oral dose of 12.5, 50, 200, or 800 ng of TCDD or [(3)H]-TCDD/kg bw on gestation day (GD) 15. Dams were sacrificed on GD16 and GD21, and the tissue concentrations of TCDD were measured in dams and fetuses. Pups were sacrificed on postnatal day (PND) 49 and PND63 for males and PND70 for females, and the reproductive effects and tissue concentrations of TCDD were determined.

RESULTSThe sex ratio (male/female) on GD21 was significantly reduced at 50 ng TCDD/kg and at 12.5 and 50 ng TCDD/kg at birth, but not at other doses. Delayed puberty was observed in males at 200 ng TCDD/kg and in males and females at 800 ng TCDD/kg. Anogenital distance, testis weight, epididymal sperm count, sperm motility, and ejaculated sperm count were not affected. Estrous cyclicity was not different from that of the control in any treatment group. A dose-dependent decrease in weight of seminal vesicle and prostate on PND49 was observed. Prostate weight was significantly decreased at 800 ng TCDD/kg. At this dose, maternal body burden and TCDD concentration in fetuses were 290 pg TCDD/g and 52 pg TCDD/g on GD16, respectively. Reduced prostate weight is a sensitive and commonly observed endpoint so that the body burdens of dams and fetuses at the LOAEL of this endpoint could be served as the basis for establishing TDI for dioxins.